This program encompasses a broad laboratory and clinical research program aimed at clarifying the mechanisms involved in heart attack (acute myocardial infarction) and ischemia (inadequate coronary blood flow) in man and experimental models, with the goal of providing a better understanding of the natural history and effects of medical and surgical therapy in patients with coronary heart disease (angina pectoris, heart attack, dysrhythmias, and cardiac failure). The experimental methods employed will include studies on ischemia in isolated tissues, acute experiments in a variety of animal preparations, studies on ischemia and infarction and their treatment in chronically instrumented, unanesthetized animals and in subhuman primates. Clinical projects will focus particularly on prediction and reduction of risk after heart attack, the effects of physical conditioning on the heart and serum lipids, exercise testing using vectorcardiographic and radionuclide methods, coronary artery spasm, and effects of vasodilators. Laboratory projects will be concerned with animal models for production and treatment of angina pectoris and sudden death, effects of exercise on coronary collaterals, use of computerized axial tomography for detecting infarcting myocardium, studies on mitochondrial enzymes, the role of the adrenergic nervous system in infarction, nucleotide metabolism in ischemia, and effects of the protaglandins on coronary vascular tone. Both the clinical and laboratory research programs will bring to bear methods such as hemodynamic and radiographic analyses, nuclear medicine, echocardiography and other noninvasive techniques, implanted ultrasonic devices, telemetry, electronmicroscopy, and basic biochemical measurements in cardiac tissues to bear on the solution of these problems.